Abstract: FR-PO079

Treatment with PD-1 Inhibitor Associated with AKI and Hypocalcemia: A Meta-Analysis of Clinical Trials

Session Information

  • AKI Clinical: Predictors
    November 03, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Manohar, Sandhya, Mayo Clinic, Rochester, Minnesota, United States
  • Kompotiatis, Panagiotis, Mayo Clinic, Rochester, Minnesota, United States
  • Thongprayoon, Charat, Bassett Medical Center, Cooperstown, New York, United States
  • Cheungpasitporn, Wisit, Mayo Clinic, Rochester, Minnesota, United States
  • Herrmann, Sandra, Mayo Clinic, Rochester, Minnesota, United States
Background

Programmed cell death protein 1 (PD-1) inhibitors, Nivolumab and Pembrolizumab, are novel agents approved for use in many cancers. However, their renal safety profiles have not yet been systematically studied. The objective of this meta-analysis was to assess the risks of electrolyte abnormalities and nephrotoxicity in patients treated with PD-1 inhibitors.

Methods

A literature search was performed using MEDLINE, EMBASE and Cochrane Database from inception through April 2017. We included clinical trials that monitored electrolyte levels and kidney functions during treatment with PD-1 inhibitors. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. The protocol for this study is registered with PROSPERO (CRD42017060579).

Results

48 clinical trials (with a total of 11,482 patients), which had electrolytes and/or serum creatinine monitored, were enrolled. The overall pooled RRs of acute kidney injury (AKI) and electrolyte abnormalities in patients treated with PD-1 inhibitors were 1.86 (95% CI, 0.95-3.64) and 1.67 (95% CI, 0.89-3.12), respectively. Compared with non-nephrotoxic controls, the pooled RR of AKI in patients treated with PD-1 inhibitors was 4.19 (95% CI, 1.57-11.18). Pre-specified subgroup analysis demonstrated a significant association between PD-1 inhibitors and hypocalcemia with pooled RR of 10.87 (1.40-84.16). The pooled estimated incidence rates of AKI and hypocalcemia in patients treated with PD-1 inhibitors were 2.2% (95%CI: 1.5%-3.0%) and 1.0% (95%CI: 0.6%-1.8%). Among patients who developed AKI with PD-1 inhibitors, the pooled estimated rate of interstitial nephritis was 16.6% (95%CI: 10.2%-26.0%). When hypocalcemia occurred after treatment with PD-1 inhibitors, the pooled estimated rate of severe hypocalcemia was 13.0% (95%CI: 3.3%-39.4%).

Conclusion

Based on the findings of our meta-analysis, treatment with PD-1 inhibitors is associated with higher risk of AKI compared with non-nephrotoxic agents. Interstitial nephritis can occur 16.6% in patients with AKI following treatment with PD-1 inhibitors. In addition, treatment with PD-1 inhibitors is also associated with hypocalcemia.